This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The mitotic spindle assembly checkpoint (SAC) is the only known checkpoint in mitosis. The SAC is composed of complex multi-signal transduction pathways that promote the proper segregation of chromosomes during cell division. As such, defects in the SAC result in chromosome instability (CIN), a hallmark of cancer. Of clinical importance, apoptosis caused by mitotic catastrophe depends on the activation of SAC. However, our knowledge of SAC signaling is far from complete, and the functional cross-talk between SAC activation and the induction of mitotic apoptosis is poorly understood. This makes it difficult to explain the mechanism by which cancer cells respond or become refractory to anti-mitotic drugs, e.g. taxol, that induced spindle-damage or mitotic catastrophe. Therefore, it is highly important to understand both the molecular mechanism by which SAC (i) controls proper chromosome segregation to maintain chromosome stability during cell division and (ii) elicits an apoptotic response in mitosis to anti-mitotic cancer therapeutic drugs.